Extended therapy with the drug Avastin, which is already used to treat several metastatic cancers, may also help women with newly diagnosed advanced ovarian cancer, according to a recent Phase III study by the Gynecologic Oncology Group (GOG). However, concerns must be addressed before it can be considered a routine treatment option.

Avastin, the brand name for bevacizumab, was FDA approved in 2004 and is used to treat breast, lung, colorectal, kidney and brain cancers. Unlike chemotherapy, which directly kills fast-growing cells, Avastin is thought to work by reducing the blood supply that tumors need to grow.

Earlier studies have shown that Avastin can help in recurrent ovarian cancer, but the new study, presented June 6 at the American Society of Clinical Oncology (ASCO) meeting in Chicago, is the first to look at the effect of the drug in newly diagnosed women.

"Early data with bevacizumab (Avastin) in patients with recurrent ovarian cancer demonstrated reductions in tumor size, elimination of fluid from the abdominal cavity and delayed tumor progression," said Michael A. Bookman, MD, Arizona Cancer Center hematology-oncology section head, who was a co-investigator in the study. "These results appeared to be at least as good as chemotherapy, and were more impressive than results in patients with other common cancers, prompting GOG to develop the carefully-designed randomized trial reported at ASCO."

The new study included 1,873 women with newly diagnosed stage III or IV ovarian, primary peritoneal or fallopian tube cancer. All the women, who had a median age of 60, had surgery to remove as much of the cancer as possible before participating in the study.

The study looked at the effect of Avastin given as a front-line treatment combined with standard chemotherapy and also as a longer-term treatment – known as maintenance therapy – given with the goal of extending survival without cancer progression.

Researchers compared the results of giving randomly assigned participants standard chemotherapy (paclitaxel plus carboplatin) with placebo and placebo maintenance, standard chemotherapy with Avastin and placebo maintenance or standard chemotherapy with Avastin plus up to 10 more months of Avastin maintenance.

"This is the only randomized trial in the world that has separately addressed the question of combined treatment as well as maintenance treatment," said Dr. Bookman, a gynecologic cancer specialist. "It allowed us to separately evaluate the impact of each."

Long-term Avastin use kept women's cancers from progressing for a median of 14.1 months, compared to a median of 10.3 months for women who received chemotherapy alone. Receiving chemotherapy with Avastin and placebo maintenance had no statistically significant benefits.

"It appears that the benefit was restricted to patients who received maintenance therapy, which is a very important observation that is already having an impact on the design of new studies," Dr. Bookman said. "It also supports earlier data showing impressive control of tumor growth in patients with recurrent disease."

However, it may be too soon to tell whether women who received extended Avastin treatment lived longer and whether the quality of their lives was improved. About 10 percent of women given long-term Avastin therapy had serious or life-threatening high blood pressure, compared with 1.6 percent of women on chemotherapy alone. About 2.3 percent of women on long-term Avastin developed severe bleeding or perforated intestines, compared with 0.8 percent of women on chemotherapy alone.

"Over the last few years, we have developed guidelines for patient selection to avoid many life-threatening complications, and we are also more experienced in managing routine side effects," Dr. Bookman said. "However, this remains an expensive treatment with the potential for serious toxicity. As such, it will be important to see clear evidence of benefit to the patient, in terms of survival or quality of life, before it can be considered routine standard-of-care for patients with newly diagnosed disease. This will be carefully evaluated in other studies."

Slowing tumor progression by nearly four months would have to be balanced against the potential side effects, inconvenience and cost of extended treatment with Avastin. The drug would cost about $72,000, according to Elizabeth A. Eisenhauer, MD, of the National Cancer Institute of Canada’s clinical trials group, who gave the public commentary on the study at the ASCO meeting.

"Dr. Eisenhauer has appropriately highlighted the promise and the challenges associated with this new treatment option," Dr. Bookman said. "We are already conducting studies using a number of agents, including bevacizumab (Avastin), to optimize results and improve outcomes for our patients."